Phosphaadamantanes: reaction with formaldehyde in acid solution

Southern Regional Research Center,1 New Orleans, La. 70179. The methoacid ... known flame retardant polymer prepared from sodium hy- droxide-neutraliz...
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Phosphaadamantanes: Reaction with Formaldehyde in Acid Solution Donald J. Daigle,* Gordon J. Boudreaux, and Sidney L. Vail Southern Regional Research Center,' New Orleans, La. 70 179

Experimental The methoacid salts of hexameihyienetetramlne, 1,3,5trlara-7-phosphaadamantane (PAA), and its oxide (PAAO) were prepared from their reaction with formaldehyde In solution containing a strong acid. The compound 2-thla1,3,5-trIara-7-phosphaadamantane 2,2-dloxide (PASO*) did not form a methoacid salt and substantlated earlier work that PASOI is chemically phosphorus oriented.

General preparation of picrate salt. The picrates of hexamethylenetetramine, PAA, and PAAO were prepared by dissolving 0.02 moles of each compound in about 100 ml of methanol and 0.02 mol of picric acid in 125 ml of ethanol. The precipitates produced were collected by filtration. 1-Hydro- l-azonia-3,5,7-triazaadamantane picrate ( I ) . Filtration yielded 6.88 g [92.7%] of crude I. The NMR spectrum (Varian A-60A spectrometer) of a deuterated dimethyl The compound 1,3,5-triaza-7-phosphaadamantane (PAA) sulfoxide solution of I at 60 MHz exhibited the following ( 7 , 2) resembles the repeating unit proposed for a wellbands relative to an internal standard (tetramethylsilane): a known flame retardant polymer prepared from sodium hysinglet at 6 4.87 and a singlet at 6 8.65in the ratio of 6:1,retetrakis(hydroxymethy1)phosphonium spectively. droxide-neutralized chloride solutions (THPOH) and ammonia. Recently, both the 1-Hydro- 1-azonia-3,s-diaza- 7-phosphaadamanfane picTHPOH-NH3 polymer and PAA were found to "decompose" rate (11). Filtration yielded 6.55 g [84.4%] of crude II. The in hot formalin, whereas the oxidized polymer and 1,3,5- NMR spectrum of a deuterated dimethyl sulfoxide solution of triaza-7-phosphaadamantane 7-oxide (PAAO) were stable to I I showed a doublet centered at 6 4.07 with a coupling consolutions of hot formalin (3). The only product isolated from stant of 9 Hz, a singlet at 6 4.78,and a singlet at 6 8.62 in the the reaction with the polymer or PAA was tris(hydroxymethratio of 3:3:1,respectively. y1)phosphine oxide. We now have isolated the products from 1-Hydro- l-azonia-3,5-diaza-7-phosphaadamantane-7the reactions of phosphaadamantanes with formaldehyde in oxide picrate (111). Filtration yielded 7.32 g (90.69'0 yield) of the presence of an acid. crude Ill. The NMR spectrum of a deuterated dimethyl sulfoxInitially, hexamethylenetetramine picrate was reacted with ide solution of 111 showed a doublet centered at 6 4.18 with a formaldehyde. With nuclear magnetic resonance spectroscocoupling constant of 1 1 , a singlet at 6 4.63,and a singlet at 6 py (NMR) the work of Foss et al. ( 4 , 5)was confirmed, and a 8.67 in the ratio of 3:3:1,respectively. methopicrate salt was proved to be the only product from General reaction conditions of picrates 1-111 with formalsuch a reaction. The product had been identified as a dimethdehyde. The picrates (0.013mol) were dissolved in a soluylpentamethylenetetramine picrate (6, 7). The NMR spectra tion in 100 ml of ethanol and formaldehyde (40 g, 37.5%, showed a 1:6 ratio of aromatic protons to methylene protons. 0.50 mol); the mixture was heated on a steam bath for the The use of dimethyl sulfoxide as a solvent interfered with the h; II, 2 h; and 111, 2 h. The solution was altime specified: I, integration of the methyl protons. lowed to cool slowly to room temperature, and the precipiThis same reaction with PAA and PAAO picrate also protate filtered. duced methopicrate salts as shown by NMR spectroscopy I-Methyl- l-azonia-3,5,7-triazaadamantane picrate ( IV). and chemical analyses. The highest theoretical yield of the Filtration yielded 3.2 g (67.3%)of crude IV. The NMR specPAA methopicrate, 45 YO (based upon PAA) (V), also suggesttrum of a deuterated dimethyl sulfoxide solution of IV showed ed that the decomposition reaction with formaldehyde might a singlet at 6 8.67,a singlet at 6 5.01,and a complex of also be operative. Yields of this reaction with hexamethylpeaks from 6 4.82to 6 4.33 in the ratio of 1:3:3.The specenetetramine and PAAO were 67 (IV) and 73% (VI), respectrum also showed a singlet at 6 2.35 (CH3 protons), but the tively. The reaction of PAAO with formaldehyde in the presprotons of the solvent overlapped, interfering in the integraence of another strong acid, hydrochloric, produced a methotion. chloride salt (VII). Apparently, acid strength is important I-Methyl- l-azonia-3,S-diaza-7-phosphaadamantane picsince in the presence of acetic acid, the reaction with either rate (V). Filtration yielded 2.34 g (45%) of crude V. The PAA or PAAO produced only the starting compounds. NMR spectrum of a deuterated dimethyl sulfoxide solution of The methopicrates of hexamethylenetetramine, PAA, and V showed a singlet at 6 2.63,a complex of peaks from 6 3.33 PAAO were also prepared in quantitative yield from methyl to 4.75,a broad singlet at 6 4.92,and a singlet at 6 8.63 in iodide salts of the three compounds and sodium picrate. respectively. the ratio of 3:8:4:2, The compound 2-thia-1,3,5-triaza-7-phosphaadamantane I-Methyl- l-azonia-3,S-diaza-7-phosphaadamantane-72,a-dioxide did not react with formaldehyde in the presence oxide picrate ( V I ) . Filtration yielded 3.95 g (73%) of crude of either picric or hydrochloric acid. However, the picrate and VI. The NMR spectrum of a deuterated dimethyl sulfoxide sochloride were isolated and by NMR spectroscopy shown to lution of VI showed a doublet centered at 6 2.88with a coube ammonium salts. pling constant of 3 Hz, a complex of peaks from 6 3.95 to 6 This work substantiates earlier work that PAA and PAAO 4.35,a broad singlet at 6 4.95,and a singlet at 6 8.67 in the resemble hexamethylenetetramine in their chemistry, that is, ratio of 3:8:4:2, respectively. they are nitrogen oriented and that PAS02 is phosphorus ori1-Methyl- l-azonia-3,5-diaza-7-phosphaadamantane-7ented. Elemental analyses obtained were in agreement with oxide chloride ( V l l ) . PAAO (6.92g, 0.04mol) was dissolved theoretical values and were submitted for review. in a solution of 100 ml of ethanol, hydrochloric acid (3.89g, 37.5%, 0.04 mol), and formalin (18.0g, 37.5%, 0.225 mol), and refluxed for 13/4 h. Evaporation of the solution at room ' One of the facilities of the Southern Region, Agricultural Research Ser- temperature and washing of the solid produced 5.5 g (61.5% yield) of crude VII. vice, U S . Department of Agriculture. 240

Journal of Chemical and Engineering Data, Vol. 21, No. 2, 1976

Alfernafive preparation of IV-VI. Compounds IV-VI were prepared by dissolving the methyl iodide salt of hexamethylenetetramine, PAA, and PAAO, respectively (0.001 mol), in methanol (60 ml) and sodium picrate (0.001 mol) in methanol (10 ml). The precipitate produced was filtered and dried. Infrared and NMR spectra of each of the compounds were identical to those of samples prepared by the other method. The methyl chloride satt of PAAO with sodium picrate also produced VI. Reaction of 2-fhia- 1,3,5-triaza-7-phosphaadamantane 2,2-dioxide ( PAS02) with formaldehyde and acid. Reaction conditions were the same as for the preparation of VII: PAS02 (2.07 g, 0.01 mol), picric acid (2.52 g, 90%, 0.01 mol), and formalin (3.0 g, 37.5%, 0.033 mol) in ethanol (150 ml). Evaporation to half volume and filtration produced 4.0 g (92.8% yield) of 5-hydro-5-azonia-2-thia-1,3-diaza-7-phosphaadamantane-2,2-dioxide picrate (VIII). The same procedure with hydrochloric acid in lieu of picric acid produced 2.0 g (82.3 YO yield) of 5-hydro-5-azonia-2-thia1,3-diaza-7-phosphaadamantane-2,2-dioxide chloride (IX). The NMR spectrum of a deuterated dimethyl sulfoxide solution showed a singlet at 6 6.83 which appears to be a mixture

of water protons and N-H since it did exchange with D20.A doublet caused by a P-H proton was not found.

MP Solvent

I 17g6



203-4 H,OEtOH

II 182-3 H,OEtOH

Ill 184-5 H,OEtOH

IV 1966

V 197-8







217.5-8.5 EtOHEtOAc

139-40 EtOH

202-3 EtOHEtOAc

Literature Cited (1) Daigle. D. J.. Pepperman, Jr., A. B., Vail, S. L., J. Heterocyci. Chem., 11, 407 (1974). (2) Daigle, D. J., Pepperman, Jr., A. B.. in review. (3) Daigle. D. J., Pepperman. Jr., A. B., Vail, S. L., in review. (4) Foss, M. E., Herst, E. L., Jones, J.K.N., Springall, H. D., Thomas, A. T., Urbanski. T.. J. Chem. SOC.,1950, p 624. (5) Foss, M. E., Herst, E. L., Jones, J.K.N., Springall, H. D.. Thomas, A T., Urbanski, T.. ibid., p 1691. ( 6 ) Graymore, J., ibid., 1931, p 1490. (7) Knudsen, P., Ber., 47, 2694 (1914). Received for review May 27, 1975. Accepted October 20, 1975

Preparation of Diethyl Formamidomalonate Arjeh B. Galun Department of Industrial Chemistry, Research & Development Authority, Ben-Gurion University of the Negev, Beer-Sheva, Israel

A rapid and convenient synthesis of diethyl formamidomalonate is described. Diethyl acetamidomalonate (3) is an important intermediate in the synthesis of a large number of amino acids. Diethyl formamidomalonate is even more suitable for this purpose owing to the much more facile hydrolysis of the formyl group. Several derivatives of tryptophan cannot be made via the acetamidomalonate, because the compounds are not stable enough to withstand the conditions required for the hydrolysis of the acetyl groups, but are smoothly synthesized using diethyl formamidomalonate. Unfortunately, the preparation of this material without high-pressure hydrogenation has been unsatisfactory. In accordance with results obtained earlier ( I ) , we found that the procedure described by Galat (2) gave erratic results. Although the reduction of the intermediate diethyl isonitrosomalonate took place, the formylation mostly failed. Therefore, it was decided to remove the water formed in the course of the reduction. The removal was carried out by azeotropic distillation with benzene. The use of benzene has the additional advantage of maintaining the reaction temperature at the desired level. This method has also been carried out on much larger scales and secures 68-70 % yields of the formylated ester.

Experimental A solution of 621 g (9 mol) of commercial sodium nitrite in 750 ml of water is added through a separating funnel to a

well-stirred mixture of 480.5 g (3 mol) of commercial diethyl malonate and 525 ml of glacial acetic acid below 5'. After the addition the cooling is terminated, and the mixture stirred for 6 h. The aqueous layer is then separated and extracted with three 300-ml portions of ether. The ethereal extracts are combined with the main fraction, and the water is separated again. The solution is dried over anhydrous magnesium SUIfate, and, after filtration, concentrated on a water bath at 20 mm. The oily residue (about 530 g) is dissolved in 2200 ml of formic acid (90% or better) and placed in a 5-1.three-neck flask equipped with an efficient stirrer and a Dean-Stark water trap. Benzene (600 ml) and 10 g of zinc powder are added, and the mixture is stirred and heated to reflux. After the reaction has started, the heating is terminated, and 405 g of zinc powder are added rapidly enough to maintain a steady reflux. The water formed is collected and removed through the trap. The hot solution is filtered 15 min after the last addition, and the solvents are removed on a water bath under reduced pressure. The residue is dissolved in 150 ml of methanol and placed in a refrigerator. The diethyl formamidomalonate separates in the form of white crystals, mp 51-52', The yield is 400-410 g (6870%). The material may be distilled in vacuo (bp 130' at 2 mm), but there is danger of decomposition.

Literature Cited (1) Ek, A., Witkop, B., J. Am. Chem. SOC., 76, 5584 (1954). (2) Galat. A,, ibid., 69, 965 (1947). (3) Zambito, A. J., Howe, E. E., Org. Synth., Coll. Vol. 3, 373 (1973). Received for review May 27, 1975. Accepted September 27, 1975

JournalofChemicalandEngineeringData, Vol. 21, No. 2, 1976